Targeted therapies in the treatment of pancreatic carcinoma

Pancreatic carcinoma is the fifth leading cause of cancer deaths in the western world. Although some progress has been made in the clinical management of pancreatic cancer, surgical resection remains the only potentially curative treatment. New strategies are urgently needed for the treatment of this disease. Advances in knowledge in genetics and molecular biology have led to the development of novel treatments targeting specific molecules. Todate, the results obtained with these new drugs have not been superior to those observed with conventional chemotherapy. In the present article we review some of the new therapies for pancreatic cancer such as the use of inhibitors of epidermal growth factor receptors, the inhibitors of metalloproteases of the extracellular matrix, the inhibitors of farnesyltransferase, and the use of anti-angiogenic treatment. MLA is supported by grant 01/9563 from the Instituto de Salud Carlos III, Madrid, Spain.     

5-Fluorouracil plus leucovorin is an effective adjuvant chemotherapy in curatively resected stage III colon cancer: long-term follow-up results of the adjCCA-01 trial.

BACKGROUND: Adjuvant postoperative treatment with 5-fluorouracil (5-FU) and leucovorin in curatively resected stage III colon cancer significantly reduces the risk of cancer recurrences and improves survival. The impact of 5-FU plus leucovorin on survival and tumor recurrence was analyzed in a long-term follow-up study in comparison with the effects of 5-FU plus levamisole in the prospective multicenter trial adjCCA-01. PATIENTS AND METHODS: Patients with a curatively resected stage III (International Union Against Cancer) colon cancer were stratified according to tumor, node and grading category and randomly assigned to receive one of the two adjuvant treatment schemes: 5-FU 400 mg/m2 body surface area intravenously in the first chemotherapy course, then 450 mg/m2 x 5 days, plus leucovorin 100 mg/m2, 12 cycles (arm A), or 5-FU plus levamisole (Moertel scheme; arm B). RESULTS: Six hundred and eighty (96.9%) of 702 patients enrolled into this study were eligible. To date, 261 patients have died, 117 on arm A and 144 on arm B (P = 0.007). After a median follow-up time of 82 months, the 5-FU plus leucovorin combination significantly improved disease-free survival [79.8 months in arm A versus 69.3 months in arm B (P = 0.012)] and significantly increased median overall survival (88.9 months in arm A versus 78.6 months in arm B; P = 0.003). Adjuvant treatment with 5-FU plus levamisole as well as 5-FU plus leucovorin was generally well tolerated; only a minority of patients experienced grade 3 and 4 toxicities. CONCLUSIONS: After curative resection of a stage III colon cancer, adjuvant treatment with 5-FU plus leucovorin is generally well tolerated. This long-term follow-up study demonstrates that adjuvant treatment with 5-FU plus leucovorin given for 12 cycles is significantly more effective than 5-FU plus levamisole (Moertel scheme) in reducing tumor relapse and improving survival.     

石门穴临床应用举隅

介绍石门穴的局部解剖、针灸方法、主治功效及其对尿路感染、小儿遗尿、妇女避孕等验案四则。     

Wnt5a在肿瘤研究中的进展

近年来研究发现WnL5a与肿瘤发生、发展关系密切.根据细胞类型不同,Wnt5a既可以起到促癌作用,又可以起到抑癌作用,其信号级联反应复杂,受多种因子调节.     

食管癌中CD44 V5和nm23-H1基因表达及意义

目的 :探讨CD4 4V5,nm2 3 H1 的基因产物表达与食管癌临床病理及预后的关系。方法 :应用免疫组织化学S P法对 85例食管癌标本进行CD4 4V5和Nm2 3 H1 的基因产物测定 ,并对其中 50例患者术后随访 3年。结果 :①CD4 4V5在食管癌中的阳性表达率为 61 .2 % ,Nm2 3 H1 在食管癌中的阳性表达率为 57.6 %。②在食管癌中CD4 4V5的过表达和Nm2 3 H1 的低表达与食管癌的浸润深度、分化程度、淋巴结转移、临床TNM分期及预后相关 (P<0 .0 5) ,而与食管癌患者的性别、年龄、肿瘤大小、病理类型均无相关性 (P >0 .0 5)。③在食管癌中 ,CD4 4V5和Nm2 3 H1 的表达呈负相关 (r=- 0 439,P <0 .0 1 ) ,且CD4 4V5的过表达伴有Nm2 3 H1 低表达者发生淋巴结转移的可能性大 (P <0 .0 1 )。结论 :CD4 4V5和Nm2 3 H1 在食管癌中的不同表达与食管癌的淋巴结转移及预后显著相关。CD4 4V5、Nm2 3 H1 的不同表达在食管癌淋巴结转移中可能起协同作用 ,可为临床预测食管癌淋巴结转移及评估预后提供重要的参考指标     

6-(1-溴乙基)-4-氯-5-氟嘧啶合成新方法

以氟乙酸乙酯为起始原料,改进抗真菌药物伏立康唑中间体6-(1-溴乙基)-4-氯-5-氟嘧啶的合成方法.该方法简化了生产工艺,降低了反应成本,反应条件温和,适合工业化生产,总收率为41.7%.     

5-羟基-1H-吲哚-3-羧酸乙酯类化合物的合成及其抗流感病毒活性

目的设计合成5-羟基-1H-吲哚-3-羧酸乙酯类化合物,评价其抗流感病毒和抗呼吸道合胞病毒活性.方法经IR、1H-NMR和MS确证目标物结构,并经体外抗病毒试验进行活性筛选.结果与结论合成了9个5-羟基-1H-吲哚-3-羧酸乙酯类化合物,初步活性试验表明,具有一定的抑制流感病毒和呼吸道合胞病毒作用,其中,化合物Ⅷ1、Ⅷ2、Ⅷ5的抗病毒活性与利巴韦林和阿比朵尔相当.     

新型抗肿瘤组蛋白去乙酰化酶抑制剂西达本胺的合成

目的:合成西达本胺{N-(2-氨基-5-氟苯基)4-[N-(吡啶-3-丙烯酰)氨甲基]苯甲酰胺}.方法:以吡啶甲醛为起始原料,通过Knoevenagel反应,制得吡啶丙烯酸,然后以N,N′-碳酰二咪唑(CDI)为催化剂,通过2步酰化反应,合成目标产物.结果:目标产物的产率为29%.结论:本法条件温和,操作简便,适合工业化生产.     

孟鲁司特对哮喘豚鼠气道嗜酸粒细胞炎症的抑制作用

目的　研究白三烯受体拮抗剂孟鲁司特 (mon telukast,MK )对哮喘豚鼠气道嗜酸性粒细胞 (Eosinophil,Eos)炎症的影响 ,探讨孟鲁司特拮抗哮喘气道炎症的可能机制。方法　以卵白蛋白致敏豚鼠制备哮喘模型。用密度梯度分离法分离并计数支气管肺泡灌洗液 (BALF)中不同密度的嗜酸性粒细胞 ;采用TUNEL技术原位检测嗜酸性粒细胞凋亡 ;通过ELISA法检测BALF中IL 5的含量 ;采用荧光酶标记法在PharmaciaUnicap 10 0System中测定BALF中嗜酸性粒细胞阳离子蛋白 (ECP)的水平。结果　孟鲁司特能降低哮喘豚鼠BALF中Eos的数量 ;在孟鲁司特治疗组 ,嗜酸性粒细胞凋亡指数明显升高 ,BALF中IL 5和ECP的含量降低 ,与模型组比较差异均有显著性。结论　降低气道IL 5和ECP的水平 ,促进嗜酸性粒细胞凋亡 ,减少嗜酸性粒细胞浸润 ,可能是白三烯受体拮抗剂孟鲁司特拮抗哮喘气道炎症的一个重要机制。